2Ammonium tetrathiomolybdate (TTM) is the treatment of choice for chronic Cu poisoning in sheep and is recommended in Wilson's disease. However, the long-term effects have not been fully evaluated and some evidence questions the long-term safety of the drug. The aim of the present study was to investigate the systemic distribution and retention of Cu and Mo in TTMtreated sheep of different breeds and Cu status. Low-Cu Cambridge sheep were divided into a TTM trial group (3.4 mg/kg, subcutaneously, on three alternate days per month, for 5 months) and a control group, and were killed at the end of the course or 7 months later. High-Cu sheep consisting of a Cu-supplemented (150 mg/kg) Cambridge group and a North Ronaldsay group were administered TTM as before and compared with untreated controls. Brain, liver, kidney, heart, skeletal muscle, pituitary, adrenals, testes and ovaries were retained for metal analysis. Mo accumulated in all organs including brain and pituitary (P < 0.02) in all TTM trial groups and was retained after cessation of treatment, except in liver, kidney and skeletal muscle. Cu was increased (P < 0.02) and retained in the cerebellum and medulla oblongata in the TTMtreated high-Cu Cambridge groups. Brain Cu v. Mo concentrations showed a strongly positive correlation (r 0.7) in the high-Cu Ronaldsay group 7 months after TTM treatment. It is concluded that TTM is not all excreted but (Mo) is widely distributed and retained in many organs including brain and pituitary. In addition TTM may redistribute some displaced excess liver Cu (Cu-TTM) to the brain. The consequences of these disturbances await clarification.

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Recent societal acceptance of cannabinoids as recreational and therapeutic drugs has posed a potential hazard to male reproductive health. Mammals have a highly sophisticated endogenous cannabinoid (ECS) system that regulates male (and female) reproduction and exo-cannabinoids may influence it adversely. Therefore it is imperative to determine their effects on male reproduction so that men can make informed choices as to their use. Here, an animal model was used to administer HU210, a synthetic analogue of Δ9-tetrahydrocannabinol (THC) and potent cannabinoid receptor (CB) agonist to determine its effects on reproductive organ weights, spermatogenesis, testicular histology and sperm motility. Its effects on the physiological endocannabinoid system were also investigated. Spermatogenesis was markedly impaired with reductions in total sperm count after 2 weeks of exposure. Spermatogenic efficiency was depleted, and Sertoli cell number decreased as exposure time increased with seminiferous tubules showing germ cell depletion developing into atrophy in some cases. Sperm motility was also adversely affected with marked reductions from 2 weeks on. HU210 also acted on the sperm's endocannabinoid system. Long-term use of exo-cannabinoids has adverse effects on both spermatogenesis and sperm function. These findings highlight the urgent need for studies evaluating the fertility potential of male recreational drug users. HU210, a selective agonist for CB1 and CB2 cannabinoid receptors impairs spermatogenesis and sperm motility and deregulates the endocannabinoid system.

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